Art of preparing alkaloid salts.



I TED STATES l ar earn WALTHER STRAUB, 0F FREIIBURG, GERMAI TY, ASSIG'NQR TO 0. E. BOEHR-INGER & SOEENE, OF MANNTIWTM-VIALDHOF, BERLIN, GERMANY.

ART PREPARING ALKA'LOID SALTS.

No Drawing.

Freibur Baden, have invented certain new 1 and use ul Improvements in the Art of Pre-' paring Alkaloid Salts; and I do hereby declare the following to be 'a full, clear, and exact'description of the invention, such as will enable others skilled in the art to which it appertains to make and use the same.

The present invention relates to the manufacture of alkaloid salts and, in particular,

of'salts containing morphin. v

The use of morphin as aremedial agent is often attended with a paralysis or disorder of the respiratory center and the ob ject of the present invention is to eliminate this undesirable property of morphin in an effectual way. It is found by me in this connection that this attendant efi'ect of morphin can be greatly reduced and even suppressed if mo'rphin is administered together with narcotin. Since it is desirable to have these alkaloids combined infixed proportions' in the product to be administered or prescribed it was my aim'to devise a method of obtaining products of this character. As a result of my. researches and experiments I have found, that alkaloid salts containing morphin and narcotin in respectively molecular proportions may be obtained if a polybasic inorganic or organic acid is caused to react on morphin and narcotin. By employing dibasic or tribasic acids, or acids of even higher basicity, forthis purpose I have obtained salts containing morphin and narcotin either in equal molecular proportions,

or in 'the proportions of one molecule of '4 morphin to two or more molecules of narcotin, or of one molecule of narcotin to two or more molecules of morphin. It will be seen, therefore, that by my inventionI am able to obtain a largevariety of chemical compounds each containing fixed proportions of morphin and narcotin, but each diifering from all the others in the relative I quantities of the two alkaloids contained therein. I l

- The new double salts' embodying one part of my invention are formed generically by causing an acid or'a salt'thereof to react on the two alkaloids, and this reaction specifically considered, may take place in various ways. For instance, Imay obtain the new compounds by evaporating an aqueous or an Specification of, Letters Patent.

7 Application filed June 15, 1912. Serial No. 703,924.

Patented May a. 1a m s.

alcoholic solution of the ingredients; by precipitatlng the same from an alcoholic solu- -tion of the ingredients by ether or by a double decomposition of their salts. The new-compounds thus produced are obtained as crystalline bodies, which are for the most part readily solublein alcohol and readily soluble in hot water. Many ofthem are also tolerably soluble in cold water. In ether and other usual organic solvents they are insoluble. The salt combining one molecule of morphin. and one molecule of narcotin with one molecule of meconic acid has been found particularly valuable for medicinal purposes.

In order to fully disclose my invention I will now describe a number of examples em bodying what I consider the preferred manner of carrying out the same. The proportions given are all, understood to be by weight.

Example 1Zlfeconazfe of morph/in and narc0tin=-254e parts of meconic acid are dissolved in about 50- parts of hot alcohol and then 3.03 parts of finely pulverized morphin and 4.13 parts of narcotin are added in succession. The whole is then filtered and the resultant salt is precipitated from the filtrate by ether. The new double salt of mor bin and narcotin is thereby obtained in the'form of uniform small white crystals which are readily soluble in water and hotalcohol. This new compound contains four molecules of water of crystallization. Its

constitution is expressed by the formula:

01H 01.CnHmNOnCmHmNO1+4HzO 826 parts of narcotin, corresponding to two molecules, The whole is then, filtered and the filtrate is evaporated at about 50, centigrade, The new salt thus obtained is solu- Win41 I blo with (nmcuity in cold water and readily .solubleinhot water and in alcohol. V

The com osition of thismew compound is {represente by the formula:

dasso u tosumso (s nsuous-mo s t .whichlwould correspond to the fondg p rcentages: 7

c-54.s%; H-sim; s-s.a5% The, percentages by actual analysiswere: i I I v C55%';' H- i5 22%; s-e;4':% 4

Exampl c3 11104 1;hin nmeotinhend dzs'ulf'omtte.4.69-part s of thebariumvsalt of phenol-disulfonic acid.are dissolved in 100- parts of waterand then aqueous'solution of 3.79 parts inorphimsulfate and @198 parts of 'ns;rcotin-su1fate is edded'tothe same; The

whole is then v.l eated f'for some time, on a water heth. 'lhe whole is thenput out-he filter to separate tzhefprecipit'eted harium= sulfate and the filtrate is evaporated 'ea'ouo; lThe neiv double" salt thus obtained is, soluble with difliculty in cold Water, but readily soluble'in alcohol and-hot Water. Its compositionis indicated by the formula ciauaon)(sognigci n uoa.fleuuuowzuso 'ods'ul fancie -31 parts of; salicyldisulfonic acidwlioseforinula is Cgl'l (GH) (COOH) (SOJH andftvhicliis described in Gaazetta cold Waterarid readily sollible'in 91501101.

a e, dissolved in pa1rts of i1ot 5% alcohol and td tlie'hotisfolutiou there are added in 3.0%1-pe'rts' of inorphin, correspondin ne mole i;;le, 8411:1826 parts narcotim cor spending to two molecules, and thereup 1eresultant solut-ion is evaporated ocean. "The newfs'alt thus obtained ,isfsolulo'le with difficulty hot or Its constitution correspondsto the formula:

In alliof the semi-series will be noted that the alkaloid nospsin oercotin are causedto, reecaon'e-polyhasw orl ii new salt so obtained iss'oluble with to form small white crystals.

genie acid, that-is to say an organic acid having two or more acid groups.

Emu/ 1e '6Sulf ate of morphin-nare more ueononueuon. csusNonHiino Y if-6 parts by Weight of morphin and 8.2

parts by Weight of ncrcotin are dissolved in 40 parts by weight of normal sulfuric acid end the Whole concentrated in oacuo.

The salt obtained is readily soluble in water and dilute alcohol and is distinguished from the mere mixture in molecular quantities of the separate sulfates by. its melting point and by its'diil'erent solubility, for instance, in water.

What I claim and desire to secure by Let ters Patent of the United States is: c

1. The process of preparinga double salt of morphin and narcotin which consists in reacting on a polybasic acid with morphin and'nar'cotim 2. The process of preparing a. double salt of merphin and narcotin which consists in reacting on e polybasicacicl with niorphin. and narcotii'i in molecular quantities, respectively. H

l 3. .The process of obtaining a douhle salt of morphin and narcotiu, which consists in! reacting on. a polybcsicacid with morphinand narcotin, end then separating the double .salt from the mixture ofthe reaction. v 4. The rocess of obtain ng a double'salt of 'morphrn and narc'otin, which consists in dissolymg meeonio acid in alcohol and adding thereto morphin and narcotin, filtering and adding ether tothe filtrate tate tliedouble salt. s

5. As a new composition of matter, a double salt in which morphin and narcotin are combined with a polyhasic acid in rcspectiv'ely molecular ounntities, said salt being soluble in fllCOlltmuIlCl insoluble in ether.

6. As a new composition of matter, a

double salt in which one molecule of inorphin and one molecule of narcotin are comshined with adibasic acid; said salt being soluble in alcohol and insoluble in ether.

7. As a new composition of matter, mcconate of morphin and narcotin having the,

. Said double salt being readily soluble in Water and hot alcohol and insoluble m ether,

and combiningwith four molecules of Water 11 testimony whereof I hereunto afiii; mysignature in the presence of two witnesses.

' WALTHER 'STRAUB. Witnesses: v v

" Geo. GIFI-ORD,

ARNOLD Zunnn. 

